Figure 2.

Involvement of viral non-structural protein amyloidogenesis in immune response blockage and spillover potential. (A) As an example of fibrillation-prone viral proteins interfering with host cell functions, Henipavirus V and W are proposed to form fibrillar filaments with properties of amyloids, either in the cytosol (for V) or the nucleus (for W) of non-bat cells, as a virulence strategy to prevent and counteract the innate immune response by acting like a “flytrap”, sequestering key cell effectors. The filaments could also be useful for the virus to recruit cellular pro-viral factors and target them to intracellular viral factories for example. (B) These filaments may further evolve into large solid-like condensates resulting in steric hindrance in the host cell, thereby trapping innate immune interactors without the need for very specific and strong interactions. In this scenario, steric hindrance would hamper the downstream actions of the innate effectors. (C) Differential ability of amyloid fibrillation by V and W between the bat reservoir and humans could be at the origin of the absence or development of pathogenesis and may be a determinant of the spillover potential of the viruses. Further details and references are provided in the text.